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B Garada

Publications and source records attributed to B Garada.

14 recordsLinked to original sources
PubMed1997

A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain.

The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide 99mTc across the blood-brain barrier in sufficient quantity to obtain in vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated 99mTc agents which can label specific transporter and receptor targets in the central nervous system.

Animals↗
PubMed1997

Functional imaging in treatment planning of brain lesions.

PURPOSE: Explore the use of functional imaging data in radiation treatment planning of brain lesions. METHODS AND MATERIALS: Compare the treatment-planning process with and without the use of functional brain imaging for clinical cases where functional studies using either single photon emission computed tomography or magnetic resonance imaging are available. RESULTS: A method to register functional image data with planning image studies is needed for functional treatment planning. Functional volumes are not simply connected regions. One activation study may produce many isolated functional areas. After finding the functional volumes and registering the functional information with the planning imaging data, the tools used for conventional three-dimensional treatment planning are sufficient for functional treatment planning. However, the planning system must provide dose-volume histograms for volumes of interest that consist of isolated pieces. Treatment plans that spare functional brain while providing identical target coverage can be constructed for lesions situated near the functional volume. However, the dose to other areas of the brain may be increased. CONCLUSIONS: Functional imaging will make determination of dose response of eloquent areas of the brain possible when combined with volumetric dose information and neuropsychological evaluation prior to and after radiation therapy. Realizing the full potential of functional imaging studies will require improved delineation of activated volumes and determination of the uncertainties in functional volume delineation. Optimization of treatment plans by minimizing dose to volumes activated during functional imaging studies should be used cautiously, because the dose to "silent," but possibly eloquent, brain may be increased.

Brain↗
PubMed1997

Focal brain dysfunction in a 41-year old man with familial alternating hemiplegia.

The acute pathophysiologic changes during hemiplegic spells and the long-term outcome of alternating hemiplegia remain obscure. In a 41-year-old male with familial alternating hemiplegia we found an increase in right frontal cerebral blood flow 3 h into a 5-h left hemiplegic episode. A repeat high-resolution brain SPECT study performed 26 h after the resolution of the left hemiplegia revealed normalization of the frontal blood flow accompanied by hyperperfusion in the right parietal lobe. An interictal SPECT scan several weeks later showed no asymmetries. Head CT and MRI scans were negative. Neuropsychologic assessment and neurologic examination revealed evidence of a diffuse disorder which predominantly involved the right hemisphere. To our knowledge, there are no previous correlative studies of serial high-resolution brain SPECT with MRI, or of detailed neuropsychologic assessment, in adult patients with such an advanced course of alternating hemiplegia of childhood.

Adult↗
PubMed1997

Neuroimaging in Closed Head Injury.

Closed head injury can be associated with significant neurologic dysfunction. Neuroimaging in this condition consists of conventional techniques such as computed tomography (CT) and magnetic resonance imaging (MR), and functional imaging studies such as single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Whereas CT and MR are sufficient to show the acute concomitants of head trauma such as extra-axial hematomas, contusions, and shear injury, functional brain imaging has been shown to play an important role in management of victims of closed head injury, particularly in the chronic stages. Detection of changes in regional cerebral blood flow associated with brain injury have been found to correlate better with neurological status and prognosis than abnormalities seen by CT or MRI.

Journal Article↗
PubMed1996

Focal cerebral perfusion defects demonstrated by 99mTc-hexamethylpropyleneamine oxime SPECT in elderly depressed patients.

High resolution single photon emission computed tomography (SPECT) was used to evaluate regional cerebral blood flow (rCBF) in 14 acutely depressed elderly patients and 29 normal subjects. SPECT images of the two groups were randomized and blindly read. Foci of decreased radionuclide uptake were assessed by number and location. The total number of rCBF defects per whole brain study was significantly greater in the depressed patients than in the normal subjects. A significantly greater number of rCBF defects was found most strikingly in the lateral frontal and less prominently in the lateral and medial temporal brain regions of the depressed patients.

Aged↗
PubMed1995

Improved regional cerebral blood flow in chronic cocaine polydrug users treated with buprenorphine.

UNLABELLED: Chronic cocaine and polydrug abuse have been associated with regional abnormalities in cerebral perfusion. The authors have previously demonstrated that these abnormalities are partially reversible after drug addiction treatment with buprenorphine. This study was designed to separate the effect on cerebral perfusion of abstinence from drug use from that of buprenorphine directly. METHODS: Fifteen cocaine- and heroin-dependent men were studied with 99mTc-hexamethylpropyleneamine oxime (HMPAO) brain SPECT. The men, all part of an inpatient drug abuse treatment research program, were randomly assigned after detoxification to receive placebo or either 6 or 12 mg daily buprenorphine treatment. SPECT studies were performed at baseline, after maximum dosage was reached and after tapering off the study drug. Studies were compared visually with regard to the number and location of perfusion defects by reviewers blinded to treatment assignment. RESULTS: Subjects receiving buprenorphine had a significant reduction in the number of defects per study between baseline and maximum buprenorphine dose as compared with those receiving placebo (decrease of 4 +/- 5.4 versus increase of 4.8 +/- 4.7, p = 0.006). These differences were dose-related. Improvement with buprenorphine was temporary, with return to baseline after tapering off. CONCLUSION: Buprenorphine treatment, and not abstinence from drug use alone, leads to improvement in regional cerebral perfusion abnormalities in chronic cocaine- and heroin-dependent men.

Adult↗
PubMed1994

Gender differences in cerebral perfusion in cocaine abuse: technetium-99m-HMPAO SPECT study of drug-abusing women.

UNLABELLED: Cocaine abuse continues to be a major public health concern, with a variety of medical and neurologic sequelae. Previous studies have demonstrated abnormalities in cerebral perfusion in chronic cocaine abusers and after acute administration of cocaine. Although women are becoming increasingly represented among drug abusers, few studies have included women. To the authors' knowledge, none has compared cerebral perfusion in asymptomatic women with that in men. METHODS: The cerebral perfusion of 13 cocaine-dependent women, 4 of whom were also heroin dependent, was studied with 99mTc hexamethylpropyleneamine oxime (HMPAO) SPECT. These women were compared with 13 cocaine-dependent men and 26 healthy control subjects. Structural brain lesions and neurologic abnormalities were excluded by MRI and neurologic evaluation. Perfusion studies were interpreted in a standardized fashion by reviewers blinded to clinical information. RESULTS: It was found that cocaine-dependent women were much less likely to have abnormal study findings than cocaine-dependent men (p = 0.003) and were indistinguishable from normal women (p = 1.0). However, the results in both women and men who concurrently used heroin plus cocaine were all abnormal. Perfusion abnormalities tended to be located in anterior brain structures, such as the frontal and temporal cortex and the basal ganglia. CONCLUSION: These data suggest that cocaine-dependent women have fewer abnormalities in cerebral perfusion than cocaine-dependent men, but that concurrent abuse of heroin and cocaine is associated with more perfusion abnormalities in both sexes.

Adult↗
PubMed1994

A neural network classifier for cerebral perfusion imaging.

UNLABELLED: Artificial neural networks have been applied to a variety of pattern recognition tasks in medical imaging and have been shown to be a powerful classification tool. The potential usefulness to discriminate normal from abnormal cerebral perfusion patterns was investigated. METHODS: Cerebral perfusion imaging with 99mTc-labeled hexamethylpropyleneimine oxime was performed on 52 normal control subjects, 29 patients with clinically diagnosed Alzheimer's disease (AD) and 25 patients with chronic cocaine polydrug abuse. Each study was registered and scaled to a common anatomic coordinate system, yielding 120 standardized cortical regions. A back-propagation neural network classifier based on regional perfusion was used to classify normal and abnormal perfusion patterns. The neural network was trained to discriminate patients with AD from age-matched normal controls and cocaine polydrug abuse patients from normal controls. The performance of the neural network in these two tasks was evaluated quantitatively by receiver operating characteristic (ROC) analysis using cross-validation. RESULTS: For patients with AD, the area under the ROC curve was 0.93 +/- 0.04. When testing with the cocaine polydrug abuser data, the area under the ROC curve was 0.89 +/- 0.04. CONCLUSION: Neural networks provide a potentially useful tool in the decision-making task to discriminate patients with AD and cocaine abuse from normal controls.

Adult↗
PubMed1993

Tc-99m HMPAO brain perfusion SPECT in acute aphasia. Correlation with clinical and structural findings.

Tc-99m hexamethylpropylene amineoxime (HMPAO) brain perfusion SPECT was correlated with CT, MRI, and clinical findings in 17 patients with acute and subacute aphasia to determine its diagnostic potential in the early phases of stroke-associated language dysfunction. SPECT was performed using a dedicated brain imaging system after intravenous injection of 20 mCi (740 MBq) of Tc-99m HMPAO. Transaxial and three-dimensional surface rendered images were evaluated visually, and perfusion defects were correlated with CT, MRI, and a standard battery of clinical tests for aphasia. Clinical examination was insufficient for anatomic localization of aphasia in more than 40% of patients. CT exams were normal in 5 patients, although SPECT demonstrated perfusion defects in all 17. Nonfluent aphasia was present in only 6 of 10 patients with perfusion defects in Broca's area and fluent aphasia was present in only 5 of 10 patients with lesions in Wernicke's area. Auditory comprehension defect was associated with perfusion defects in the inferior parietal region in 9 of 12 patients (P = 0.05); reading and writing abnormalities were associated with perfusion defects in the posterior frontal, superior and inferior parietal cortex, and superior temporal gyri, and repetition deficit was associated with defects involving the inferior parietal cortex, the supramarginal and angular gyri, and the ipsilateral thalamus in 8 of 11 patients (P < 0.05). Brain perfusion SPECT should be included in the initial evaluation of aphasic patients, because clinical tests of aphasia and morphological imaging have limited value for accurately determining the extent and location of functional deficits.

Acute Disease↗
PubMed1993

Quantitative brain SPECT in Alzheimer's disease and normal aging.

To improve the diagnostic utility of brain single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD), we have developed and evaluated an objective method of differentiating patients and healthy elderly controls using a quantitative image analysis protocol. HMPAO-SPECT image datasets from 29 patients with probable AD and 78 age-matched controls were registered to a common anatomic frame of reference. Activity levels within 120 standardized cortical volumes were determined by an automated procedure. Subjects were classified into normal and AD groups by quadratic discriminant analysis using two features: global average activity level and average normalized activity levels within the two clusters of standardized volumes identified as most significantly different in AD by analysis of covariance. The classification used split-half replication to ensure valid results. Classification performance quantified by the area under a binormal ROC curve fitted to the data was 0.923 +/- 0.036; at a threshold likelihood ratio of 1, the sample sensitivity was 91% and specificity was 86%. We conclude that quantitative SPECT accurately distinguishes AD patients from elderly controls.

Aged↗
PubMed1993

Regional cerebral blood flow improves with treatment in chronic cocaine polydrug users.

Brain perfusion is abnormal in chronic cocaine users. To determine whether these perfusion abnormalities are reversible following treatment, we studied 10 cocaine-dependent polydrug users with 99mTc-HMPAO SPECT 2 to 3 days after admission to an inpatient treatment facility and at 7 to 8 days and 17 to 29 days after abstinence from drugs. The patients also received buprenorphine, an opioid mixed agonist-antagonist, beginning 10 days after admission and continuing to the end of the study. Imaging began 10-15 min after injection of 99mTc-HMPAO (20 mCi) using an annular gamma camera system. MRI was performed during hospitalization using a 1.5 Tesla system. SPECT and MRI were merged and five axial SPECT slices centered at the level of the basal ganglia were selected for analysis. Activity ratios were derived for cortical regions relative to cerebellar activity and were corrected for linearity with respect to regional cerebral blood flow. The cortical regions were classified as abnormal (activity ratio < 0.6), borderline (0.6-0.72) and normal (> 0.72) based on the results of the first SPECT study. In abnormal zones, regional cerebral blood flow (rCBF) increased 11.0% +/- 9.0% at 7 to 8 days and 23.8% +/- 9.4% at 17 to 29 days after initiation of treatment. The increase in rCBF was 4.8% +/- 7.1% (7 to 8 days) and 11.1% +/- 8.0% (17 to 29 days) in borderline cortex and decreased 2.9% +/- 6.3% (7 to 8 days) and increased only 2.7% +/- 13.4% (17 to 29 days) in normal cortex. The increase in rCBF did not vary significantly by location. The perfusion defects observed in chronic cocaine polydrug users are partially reversible with short-term abstinence and buprenorphine treatment.

Adult↗
PubMed1992

Hypertensive encephalopathy: findings on CT, MR imaging, and SPECT imaging in 14 cases.

Hypertensive encephalopathy is a syndrome consisting of headache, seizures, visual changes, and other neurologic disturbances in patients with elevated systemic blood pressure. The purpose of this study was to analyze the imaging findings in 14 patients with hypertensive encephalopathy. CT (n = 13), MR (n = 12), and single-photon emission computed tomography (n = 2) examinations performed in these patients before and after resolution of symptoms were reviewed. Eight had the preeclampsia-eclampsia syndrome, and six had hypertensive encephalopathy due to other causes. CT and MR findings in all patients having these examinations were indicative of edema in the cortex and subcortical white matter in the occipital lobes. Two of the 14 patients also had similar findings in the cerebellum and frontal lobes. Single-photon emission computed tomography showed increased vascular perfusion adjacent to areas that appeared abnormal on CT and MR. The findings on the imaging studies resolved on follow-up examinations performed after the hypertension was corrected. Our results suggest that the radiologic findings associated with hypertensive encephalopathy may be useful in establishing the diagnosis in the appropriate clinical setting.

Adolescent↗
PubMed1992

A comparison of brain perfusion SPECT in cocaine abuse and AIDS dementia complex.

Intravenous drug use is a major risk factor for HIV-1 infection. Since both AIDS dementia complex (ADC) and cocaine have been associated with abnormal brain perfusion imaging, we compared the scintigraphic patterns of ADC patients and cocaine polydrug users with normal control subjects using 99mTc-HMPAO SPECT. We found a high incidence of cortical defects in both ADC (100%) and cocaine-dependent (90%) subjects. In the cocaine and ADC patients, cortical defects were most frequent in the frontal, temporal and parietal lobes and occurred with similar frequency in the two populations. In both groups, the number of cortical defects per subject was higher than normal subjects (10.0 +/- 5.0 for ADC, 10.1 +/- 5.2 for cocaine and 0.7 +/- 1.5 for normal), background activity was high (a 65% and 60% incidence for ADC and cocaine, respectively), and basal ganglia involvement was frequent (40% and 65% for ADC and cocaine). We conclude that the brain perfusion pattern, while a sensitive indicator of ADC, cannot be distinguished from chronic cocaine polydrug use and caution should therefore be applied before entertaining a specific diagnosis.

AIDS Dementia Complex↗